Approval Letter Other 761225 (Jan 1, 2024)

Summary

This is a Complete Response Letter from the FDA to Hugel, Inc. regarding their Biologics License Application (BLA) for letibotulinumtoxinA injection. The FDA has determined that the application cannot be approved in its present form due to several deficiencies, including unresolved facility inspection issues, pending labeling comments, and requirements for a comprehensive safety update.

Key points

• Satisfactorily resolve deficiencies identified during the inspection of the Hugel, Inc. manufacturing and testing facility (FEI 3012163998).
• Review labeling review resources, including Prescription Drug Labeling Resources, Pregnancy and Lactation Labeling Final Rule websites, and the Selected Requirements for Prescribing Information (SRPI) checklist.
• Resubmit the proposed proprietary name (Letybo) when responding to the application deficiencies.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
• The safety update must describe in detail any significant changes or findings in the safety profile.
• The safety update must incorporate new safety data from studies/clinical trials for the proposed indication, presenting it in the same format as the original submission.
• The safety update must present tabulations of new safety data combined with the original application data.
• The safety update must include tables comparing frequencies of adverse events in the original application with retabulated frequencies.

Cited reasons

• Unresolved Manufacturing Facility Deficiencies
• Reserved Comment on Proposed Prescribing Information
• Reserved Comment on Proposed Carton and Container Labeling
• Resubmission of Proprietary Name
• Comprehensive Safety Update Required
• The application cannot be approved in its current form due to unresolved manufacturing facility deficiencies. Additionally, the agency has reserved comments on proposed labeling until other issues are resolved and requires a comprehensive safety update upon resubmission.

Recommended actions

• Satisfactorily resolve deficiencies identified during the inspection of the Hugel, Inc. manufacturing and testing facility (FEI 3012163998).
• Review labeling review resources, including Prescription Drug Labeling Resources, Pregnancy and Lactation Labeling Final Rule websites, and the Selected Requirements for Prescribing Information (SRPI) checklist.
• Resubmit the proposed proprietary name (Letybo) when responding to the application deficiencies.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
• The safety update must describe in detail any significant changes or findings in the safety profile.
• The safety update must incorporate new safety data from studies/clinical trials for the proposed indication, presenting it in the same format as the original submission.
• The safety update must present tabulations of new safety data combined with the original application data.
• The safety update must include tables comparing frequencies of adverse events in the original application with retabulated frequencies.

Deficiency summary

The application cannot be approved in its current form due to unresolved manufacturing facility deficiencies. Additionally, the agency has reserved comments on proposed labeling until other issues are resolved and requires a comprehensive safety update upon resubmission.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA

Impact

Impact score

0.95

Estimated delay

450 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary barrier to approval is unresolved manufacturing facility deficiencies, necessitating a complete resubmission that also includes a comprehensive safety data update and addresses pending labeling comments.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%